The study will include participants with moderate to severe Crohn's disease. The aim is to evaluate the safety, tolerability, and efficacy of anti-oncostatin M monoclonal antibody (mAb) GSK2330811. This is a parallel group study with Induction and Maintenance periods. During Induction, the first 100 participants randomised will receive a 450mg GSK2330811 SC loading dose followed by 150mg weekly (Q1W), or placebo for 12 weeks. Additional dose-ranging arms will open after the 100th participant is randomized and in addition to placebo and the highest dose arms will also include a 300mg subcutaneous (SC) loading dose followed by 150mg SC every 2 weeks (Q2W) arm, a 300mg loading dose followed by 150mg SC every 4 weeks (Q4W) arm and a 150mg SC every 8 weeks (Q8W) arm. Participants with a clinical response at Week 12 will continue into a 40-week blinded maintenance period and will receive either 150mg SC Q2W, 150mg SC Q4W, 150mg SC Q8W or placebo. Participants without a clinical response at Week 12 will be offered up to 40 weeks of open label treatment with GSK2330811. Approximately 560 participants will be screened to randomize 280.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
GSK2330811 will be available as SC injection with a unit dose strength of 150 mg/mL. GSK2330811 will be available in single-use pre-filled syringe.
Placebo will be available as SC injection of 0.9 percent saline solution. It will be available as single-use pre-filled syringe.
Percentage of participants with endoscopic response measured by Simple Endoscopic score for Crohn's Disease (SES-CD) at Week 12
The SES-CD is a validated tool for grading the endoscopic severity of active Crohn's disease based on an assessment of the size of individual ulcers, the proportion of the surface that is abnormal and the proportion of the surface that is ulcerated, and the presence or absence of visible stenosis. The attributes are scored across 5 bowel segments and combined to give an SES-CD score ranging from 0 to 56 (higher scores represent more severe endoscopic disease involvement). SES-CD will be determined for each endoscopy using a central reading algorithm. Endoscopic response is defined as \>= 50 percent decrease from Baseline in SES-CD
Time frame: Week 12
Percentage of participants with endoscopic response based on dose response relationship at Week 12 measured by SES-CD
The SES-CD is a validated tool for grading the endoscopic severity of active Crohn's disease based on an assessment of the size of individual ulcers, the proportion of the surface that is abnormal and the proportion of the surface that is ulcerated, and the presence or absence of visible stenosis. The attributes are scored across 5 bowel segments and combined to give an SES-CD score ranging from 0 to 56 (higher scores represent more severe endoscopic disease involvement). SES-CD will be determined for each endoscopy using a central reading algorithm. Endoscopic response is equivalent to \>= 50 percent decrease from Baseline in SES-CD
Time frame: Week 12
Change from Baseline in SES-CD at Week 12
The SES-CD is a validated tool for grading the endoscopic severity of active Crohn's disease based on an assessment of the size individual ulcers, the proportion of the surface that is abnormal and the proportion of the surface that is ulcerated, and the presence or absence of visible stenosis. The attributes are scored across 5 bowel segments and combined to give an SES-CD score ranging from 0 to 56 (higher scores represent more severe endoscopic disease involvement). SES-CD will be determined for each endoscopy using a central reading algorithm
Time frame: Baseline (within 35 days prior to Day 1) and Week 12
Percentage of participants in endoscopic remission at Week 12
Endoscopic remission will be equivalent to SES-CD \<=4 and \>=2 point reduction from Baseline, and no sub-score \> 1 in any individual score
Time frame: Week 12
Percentage of participants with absence of mucosal ulceration on endoscopy at Week 12
Endoscopy mucosal healing will be assessed during central endoscopic reading of the ileo-colonoscopies where absence of mucosal ulceration will be noted
Time frame: Week 12
Percentage of participants with clinical response measured by Patient Reported Outcome 2 (PRO2) at Week 12
Participants will record the following items related to patient reported symptoms/outcomes information electronically on a hand-held device at home during the study: Abdominal pain (AP) in the past 24 hours (scored from 0 to 3: 0 = none, 1 = mild, 2 = moderate and 3 = severe); Number of liquid or very soft stools (stool frequency; SF) in the past 24 hours. Clinical response will be defined as \>=30 percent reduction from Baseline in average daily SF or \>=30 percent reduction from Baseline in average daily AP, with both not worse than Baseline.
Time frame: Week 12
Percentage of participants in clinical remission at Week 12 measured by PRO2
Participants will record the following items related to patient reported symptoms/outcomes information electronically on a hand-held device at home during the study: Abdominal pain (AP) in the past 24 hours (scored from 0 to 3: 0 = none, 1 = mild, 2 = moderate and 3 = severe); Number of liquid or very soft stools (stool frequency; SF) in the past 24 hours. Clinical remission is defined as average daily SF \<=3 and average daily AP \<=1, with both not worse than Baseline
Time frame: Week 12
Change from Baseline in serum C-reactive protein at Week 12
Serum samples will be collected at indicated timepoints for the analysis of changes from Baseline of C-reactive protein.
Time frame: Baseline (Day 1) and Week 12
Change from Baseline in fecal calprotectin at Week 12
Change from Baseline of fecal calprotectin will be assessed by collecting fecal samples at the time-points
Time frame: Baseline (Day 1) and Week 12
Plasma concentration of GSK2330811
Blood samples will be collected at indicated timepoints for analysis of plasma concentration of GSK2330811
Time frame: Pre-dose on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 10, and 12
Area Under the Concentration Time Curve Over the Dosing Period (AUC [0-tau]) of GSK2330811
Blood samples will be collected at indicated timepoints for analysis of AUC (0-tau) of GSK2330811
Time frame: Pre-dose on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 10, and 12
Trough Concentration at steady state (Ctrough ss)
Blood samples will be collected at indicated time-points for analysis of Ctrough ss of GSK2330811
Time frame: Pre-dose on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 10, and 12
Serum levels of free Oncostatin M (OSM)
Blood samples will be collected at indicated timepoints for analysis of free OSM levels in serum.
Time frame: Pre-dose on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 10, and 12
Serum levels of total OSM
Blood samples will be collected at indicated timepoints for analysis of total OSM levels in serum.
Time frame: Pre-dose on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 10, and 12
Number of participants with anti-drug antibodies
Blood samples will be collected at indicated timepoints for analysis of anti-drug antibodies
Time frame: Pre-dose on Day 1 and Weeks 4, 8 and 12
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